Two main findings, made in our laboratories, form the base of this project. First, a mutant strain of mice has been obtained by crossbreeding hereditarily athymic and hereditarily asplenic mice. The resulting hybrid has no thymus or spleen, and is referred to hereinafter as the "LASAT" mouse. The lasat mouse is an ideal model for heterotransplantation of human malignancies, because of the absence of cellular immunity and the extremely low amount of immunoglobulins produced. Second, we have developed unique malignant cell-lines of human origin such as chronic myelogenous leukemia (CML) cells with the Philadelphia (Ph1) chromosome and multiple myeloma (MM) cells which are producing the same lambda Bence Jones protein found in the patient. These two cell-lines as well as other unique cell systems are being used in the heterotransplantation experiments proposed in this application because the transplantation of myelogenous leukemic cells have not been achieved prior to our experiments. We have now sucessfully grown CML and other blood cells in lasat mice. Therefore, we propose to expand and characterize the colony of athymic-asplenic animals for heterotransplantation of human cancers as follows: 1) to determine the immunocompetence of lasat mice by studying cellular and humoral immunity to thymus dependent and non-dependent antigens, 2) grafting or normal and abnormal allogeneic and xenogeneic tissues, 3) to characterize the lymphopoietic system of the lasat mouse using various histopathologic techniques, and 4) to study the hematopoiesis of athymic-asplenic mice. The long-term goal is to use and make available this unique animal model for a number of immunobiologic studies and experiments of tumor immunology. BIBLIOGRAPHIC REFERENCES: Lozzio, B.B., Machado, E.A., Lozzio, C.B. and Lair, S.V. Hereditary asplenic-athymic mice: transplantation of human myelogenous leukemic cells. J. Exp. Med. 143:225-231, 1976. Lozzio, B.B., Lozzio, C.B. and Machado, E.A. Human myelogenous (Ph1+) leukemic cell line: transplantation into athymic mice. J. Natl. Canc. Inst. 56 (May), 1976.